The spinal cord muscle culture provides as reliable model system of organotypic neuromuscular development and maturation. The experimental program will be directed toward utilizing this in vitro model and manipulating it to obtain a better understanding of physiological and metabolic mechanisms underlying the development and maintenance of normal neuromuscular relationships. Trophic influences of neurons and supporting cells will be investigated in regard to the formation of, and in direct relation to the neuromuscular junction. The cultures will be exposed to experimental conditions designed to impair or interrupt normal functional nerve muscle interrelationships without causing overt damage to either of these components. Coordinated cytologic, histochemical, electrophysiologic and electromicroscopic studies will be made on cord-muscle cultures following application of selective pharmacologic agents, e.g. anticholinergic drugs, local anesthetics and other neural depressants, as well as agents affecting axoplasmic transport and mitochondrial function. The functional competence of anterior horn cells may be altered through microsurgical lesions of specific regions of the neural complex. Attempts will also be made to examine factors which may mimic neurotrophic influence on muscle and prevent or retard muscle atrophy after denervation, e.g. sympathetic and CNS neurons, neural tissue extracts and specific chemical agents, and directly induced muscle contractions. BIBLIOGRAPHIC REFERENCES: Crain, S.M. and Peterson, E.R. Development of specific sensory-evoked synaptic networks in fetal mouse cord-brainstem cultures. Science 188: 275, 1975. Hamburgh, M., Peterson, E., Bornstein, M., and Kirk, C. Capacity of fetal spinal cord obtained from dystrophic mice (dy2J) to promote muscle regeneration. Nature 256: 219, 1975.